This invention relates to an apparatus for testing the inhalation toxicity of chemical agents such as agricultural chemicals on small animals such as rats, and more particularly, to such an apparatus for exposing the noses or heads of animals to the mist of a test liquid so that the animals may inhale the mist.
In general, inhalation toxicity test are performed by exposing rats or other small test animals to the mist of an agent to be tested, that is, a dispersion of droplets of a test agent in air or another suitable gas when the test agent is liquid, or a dust or fume in which particles of a test agent are dispersed in air or another suitable gas when the test agent is solid, or air containing a gaseous test agent. The influence of the test agent inhaled on test animals is observed to evaluate the toxicity of the agent. The typical inhalation toxicity test is an acute inhalation toxicity test wherein the toxicity of a chemical agent is usually evaluated in terms of the concentration of the agent at which one-half of test animals are killed upon exposure for a predetermined time (that is, median lethal concentration LC.sub.50).
In these inhalation toxicity tests, the chemical agent inhaled in the form of mist reaches the lung of a test animal by way of its nasal or oral cavity and air-passages (trachea and bronchial tube). Thus, the inhaled agent is deposited on the nasal or oral cavity and air-passages as well as the lung. The distribution of the agent deposited on these organs widely varies with the size of droplets or particles when the agent is in the form of mist or dust. In general, the majority of relatively large size droplets or particles deposit on the nasal or oral cavity while the minority reach the lung. The smaller the size of droplets or particles, the more they reach the lung. The minority of relatively small size droplets or particles deposit on the nasal or oral cavity while the majority reach the lung. The influence of a chemical agent on an animal varies depending on a particular organ on which the inhaled agent is predominantly deposited. Test animals which are exposed to mists of the same agent at an equal concentration in different runs are affected to a different degree or in a different way if droplets in the mists are different in size for each run. Then, when acute inhalation toxicity tests are repeated using the same agent, the results or median lethal concentration values will show a variation depending on the size of droplets and the distribution thereof. Conversely, even when median lethal concentration values are equal, these values must be compensated with respect to the droplet size and its distribution before the true toxicity of an agent can be determined. For these reasons, in order that accurate toxicity evaluation is achieved in inhalation toxicity tests, particularly those tests using mist, the mist to which test animals are exposed must have a controlled droplet size distribution, particularly a uniform droplet size distribution in which the droplet size is less than a given value. The mist is preferably free of unexpectedly large size droplets.
The inhalation toxicity test may be performed in two methods, full and local exposure methods. In the full exposure method, a rat or another small animal is fully exposed to the atmosphere of a chemical agent. In the local exposure method, only the head or nose of an animal is exposed. The latter is preferred to correctly evaluate the inhalation toxicity of an agent because the agent is percutaneously taken in by the animal in addition to the inhalation through the respirator in the former method.
One example of prior art apparatus for use in inhalation toxicity tests according to the local exposure method is illustrated in FIG. 5. This apparatus comprises a vertical, hollow cylindrical housing 1 defining an inhalation chamber therein. The side wall of the housing 1 includes a plurality of circumferentially spaced-apart openings 2 to each of which a holder 4 for holding a test animal is attached such that the head or nose of the animal is faced to the chamber. Located at the top 1A of the housing 1 is means for supplying the mist of a test agent, for example, a spray nozzle 5 for atomizing a test liquid. The heads or noses of test animals are thus exposed to the mist flowing down the chamber as shown by dot-and-dash line arrows. The use of the spray nozzle 5 is insufficient to provide the mist with a uniform droplet size distribution. There often occur variations in droplet size and such variations are inconsistent in successive runs. Further some fine droplets impinge or contact with each other to coalesce into relatively large size droplets before they are inhaled by the animals during the downward travel from the nozzle 5 to the openings 2. That is, the mist that the animals inhale usually has a widely varying droplet size distribution and tends to contain unexpectedly large size droplets. It is thus difficult to achieve accurate toxicity evaluation. The mist may be passed through a classifier to provide a uniform droplet size distribution before it is introduced into the chamber. It is still difficult to avoid the tendency that fine droplets coalesce into relatively large size droplets during the downward travel from the top to the openings or before the mist is inhaled by test animals. In addition, even after relatively large size droplets have been removed from the mist by the classifier, droplets can coalesce into large size droplets during the travel from the classifier to the inlet of the chamber. It is thus difficult to prevent unexpectedly large size droplets from being inhaled by test animals.
It is, therefore, a primary object of the present invention to provide an inhalation toxicity testing apparatus in which test animals are exposed to the mist of a test liquid with unexpectedly large size droplets removed, thereby ensuring accurate toxicity evaluation.
Another object of the present invention is to produce the mist of a test liquid which has a controlled or uniform droplet size distribution upon exposure of test animals thereto, thereby achieving more accurate toxicity evaluation.
A further object of the present invention is to produce the mist of a test liquid having a uniform concentration and a uniform droplet size distribution when an inhalation test is simultaneously performed on a plurality of test animals.
A still further object of the present invention is to reduce the amount of a test liquid consumed in vain.